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Craniofacial Development and Disease

颅面发育与疾病

基本信息

批准号：
8677589
负责人：
Paul Trainor
金额：
$ 39.35万
依托单位：
STOWERS INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8677589
关键词：
Accounting Animal Model Apoptosis Apoptotic Budgets Cartilage Cell Death Cell Maintenance Cells Centers for Disease Control and Prevention (U.S.)Child Cleft Lip Cleft Palate Congenital Abnormality Connective Tissue Counseling Craniofacial Abnormalities Craniosynostosis Data Defect Dental Care Destinations Development Disease Embryo Embryonic Development Employee Strikes Esthetics Etiology Event Exhibits Face Future Gene Proteins Genes Genetic Genotype Head Healthcare Human Individual Infant Mortality Knockout Mice Maintenance Mandibulofacial Dysostosis Maps Modeling Mus Names Nerve Tissue Neural Crest Neural Crest Cell Nuclear Orphan Receptor Operative Surgical Procedures Parents Pathogenesis Pattern Peripheral Nervous System Play Population Prevention Process Rehabilitation therapy Robin bird Role Severities Shapes Stem cells Syndrome Therapeutic Tissues Waardenburg syndrome X Chromosome bone chromatin immunoprecipitation clinical application cost craniofacial disorder prevention epithelial to mesenchymal transition life time cost loss of function malformation migration mouse model mutant nerve stem cell neural plate novel novel therapeutics pluripotency prevent psychologic social stable cell line stem

项目摘要

DESCRIPTION (provided by applicant): In order to minimize and prevent craniofacial anomalies, it is essential to understand the specific cause of individual malformation syndromes. However, this requires a deep appreciation of the normal developmental events that shape head and facial development during embryogenesis. The majority of the tissues of the head and face including bone, cartilage, connective and peripheral nervous system tissue are derived from a cell population called the neural crest. Most craniofacial syndromes are thought to occur due to a defect in the neural crest cell development during embryogenesis. Thus it is essential to study how and when neural crest cells are formed, what guides neural crest cells to their final destinations, what keeps neural crest cells alive and also how neural crest cells decide to become cartilage or bone of connective and nerve tissue. In this proposal we study a mouse model of Treacher Collins syndrome, which replicates the severe craniofacial disorder in humans. Treacher Collins syndrome arises due to a developmental defect occurring during embryogenesis in which insufficient neural crest cells are generated to make a normal head and face. We have identified a broad mechanism by which we can prevent the development of craniofacial anomalies typical of Treacher Collins syndrome and in this proposal we refine this process to facilitate future clinical applications. In addition, since our mouse model of Treacher Collins syndrome represents one of few mouse animal models that exhibit a defect in neural crest cell formation, we have used this model to identify new genes that are important for neural crest cell and craniofacial development. For the purpose of this proposal we focus on one gene, called Nr6a1, which appears to be critical for the neural crest cell formation process and as such is essential for normal craniofacial development.

描述（由申请人提供）：为了尽量减少和预防颅面异常，有必要了解个体畸形综合征的具体原因。然而，这需要深入了解胚胎发生过程中塑造头部和面部发育的正常发育事件。头部和面部的大部分组织，包括骨骼、软骨、结缔组织和周围神经系统组织，都源自称为神经嵴的细胞群。大多数颅面综合征被认为是由于胚胎发生过程中神经嵴细胞发育缺陷而发生的。因此，有必要研究神经嵴细胞如何以及何时形成，什么引导神经嵴细胞到达最终目的地，什么使神经嵴细胞保持活力，以及神经嵴细胞如何决定成为结缔组织和神经组织的软骨或骨骼。在这项提案中，我们研究了特雷彻柯林斯综合征的小鼠模型，该模型复制了人类的严重颅面疾病。特雷彻柯林斯综合征是由于胚胎发生过程中发生的发育缺陷而产生的，其中产生的神经嵴细胞不足以形成正常的头部和面部。我们已经确定了一种广泛的机制，可以通过它来预防特雷彻柯林斯综合征典型的颅面异常的发展，并且在本提案中，我们改进了这一过程以促进未来的临床应用。此外，由于我们的特雷彻柯林斯综合征小鼠模型是少数表现出神经嵴细胞形成缺陷的小鼠动物模型之一，因此我们使用该模型来识别对神经嵴细胞和颅面发育重要的新基因。出于本提案的目的，我们重点关注一个名为 Nr6a1 的基因，该基因似乎对神经嵴细胞形成过程至关重要，因此对于正常颅面发育至关重要。

项目成果

期刊论文数量（59）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cranial nerve development requires co-ordinated Shh and canonical Wnt signaling.

DOI：
10.1371/journal.pone.0120821
发表时间：
2015
期刊：
PloS one
影响因子：
3.7
作者：
Kurosaka H;Trainor PA;Leroux-Berger M;Iulianella A
通讯作者：
Iulianella A

Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation.

DOI：
10.1038/ncomms10328
发表时间：
2016-01-21
期刊：
Nature communications
影响因子：
16.6
作者：
Sakai D;Dixon J;Achilleos A;Dixon M;Trainor PA
通讯作者：
Trainor PA

Developmental biology is "Cruzing".

发育生物学是“Cruzing”。

DOI：
10.1016/j.devcel.2004.09.011
发表时间：
2004
期刊：
Developmental cell
影响因子：
11.8
作者：
Trainor,PaulA
通讯作者：
Trainor,PaulA

Application of lacZ transgenic mice to cell lineage studies.

lacZ转基因小鼠在细胞谱系研究中的应用。

DOI：
10.1007/978-1-60327-483-8_10
发表时间：
2008
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
0
作者：
Watson,CatherineM;Trainor,PaulA;Radziewic,Tania;Pelka,GregoryJ;Zhou,SheilaX;Parameswaran,Maala;Quinlan,GabrielA;Gordon,Monica;Sturm,Karin;Tam,PatrickPL
通讯作者：
Tam,PatrickPL

Facial dysostoses: Etiology, pathogenesis and management.